[EMBARGOED UNTIL 6/1/2023] Ticks are globally renowned vectors for numerous zoonoses. Ixodid ticks transmit a variety of viral, bacterial, and protozoan pathogens to their vertebrate hosts. Because of the expansion of the geographic ranges of both ticks and pathogens, increasing tick populations, emerging tick-borne pathogens and continued challenges of achieving effective and sustained tick control, ticks and tick-borne diseases have increased in importance from medical and veterinary public health perspectives. Host immune resistance to ticks has been studied since the first half of the 20th century. This dissertation addresses (i) adaptation of a naturally coevolved large-animal model to investigate immunological underpinnings of resistance to tick challenge, (ii) interference with experimental biologic transmission of a naturally coevolved tick-borne pathogen, Anaplasma marginale, to cattle, (iii) preliminary observations of effects of tetracycline on acquisition and transmission of A. marginale by tick vectors and (iv) preliminary optimization of artificial feeding conditions for ixodid ticks with different apparatuses. Several tick proteins were identified, which were reactive to antisera of tick-extract-immune cattle that were associated with reduced tick performance. The proteins identified here are important for future experiments to determine their posited roles in reduction of tick feeding. Dermacentor andersoni and D. variabilis ticks, natural biologic vectors of A. marginale in the United States, did not experimentally transmit this pathogen to susceptible hosts immunized with crude homogenates of tick tissues. In addition to the main emphasis of this dissertation, preliminary observations included reductions in infection levels acquired by ticks and effects of tetracycline on tick acquisition and transmission of A. marginale. Collectively, the work described in this dissertation suggested that interventions with acquisition and transmission of A. marginale and other tick-borne pathogens are not necessarily dependent on tick mortality.